In the biomedical field, devices are known for the distribution or containment of biological substances, like proteins, enzymes, antibodies, antigens, DNA, and the like, dissolved in solutions or biological fluids.
Such biomedical devices are manufactured by assembling different components of different materials by adhesive compositions. Several patents and patent publications describe such a kind of devices.
U.S. Pat. No. 5,338,688 describes a device for ejecting biological fluids comprising a reservoir connected with an ejection chamber provided with a heating element. U.S. Pat. No. 4,877,745 describes a similar device, wherein the ejection chamber is provided with a piezoelectric element.
U.S. Pat. No. 6,830,621 describes a liquid discharge apparatus comprising (i) a liquid holding portion for holding the probe liquid, (ii) a supply opening for supplying the probe liquid to the liquid holding portion, (iii) a liquid discharging nozzle for discharging the probe liquid, and (iv) a flow path connecting the nozzle with the liquid holding portion. The nozzle openings and the supply opening are disposed on mutually opposed faces of the apparatus. The apparatus has a laminated structure composed of a first plate-shaped member in which said nozzles are formed, and a second plate-shaped member in which said plurality of liquid supply opening are formed, and intermediate plate-shaped members in which the flow path connecting the nozzle with the liquid holding portion is realized.
EP 1,933,138 discloses microarrays of capture probes on a substrate to be used in biological assays, for instance to examine analyte biological fluids, such as human blood or tissue samples, for the presence and/or concentration of certain bacteria, viruses and/or fungi. The capture probes have a selective binding capacity for a predetermined indicative factor, such as a protein, DNA or RNA sequence. In the microarray technique, a set of specific capture probes, each of which being chosen in order to interact specifically (e.g. hybridize in the case of a DNA microarray) with one particular target biological compound, are immobilized at specific locations of a biosensor solid substrate, for instance by printing. Suitable probes may comprise bio-fluids containing the specific indicative factor, for instance a solution of a specific DNA sequence and/or antibody. After the substrate has been provided with the capture probes, for instance by printing them on the substrate using an ink jet device, the analyte fluid is forced to flow through the substrate, or is forced to flow over the substrate. In order to be able to visualize the presence of an indicative factor in the analyte fluid, molecules of the analyte fluid may for instance be provided with fluorescent and/or magnetic labeling. In case of an ELISA (enzyme-linked immunosobent assay) an enzyme is attached to the second antibody, instead of a radiolabel. An intensely colored or fluorescent compound is then formed by the catalytic action of this enzyme. The labeled molecules of the analyte fluid adhere to those capture probes of the substrate that have binding capacity for the molecule considered. This results in a detectable fluorescence on the spot the specific factor adheres to, at least when using fluorescent labeling. The captured molecules are typically read by illumination with a light source, and the fluorescent pattern recorded with the aid of a CCD camera for instance. The recorded pattern is a characteristic of the presence of a bacterium or a set of bacteria. By providing capture probes with different specificity for different factors, the array may be used to assay for various different factors at the same time. Using such arrays enables high-throughput screening of analyte fluids for a large amount of factors in a single run.
U.S. Pat. No. 5,932,315 discloses a microfluidic structure assembly having a microchannel formed by bonding two plates together. The microfluidic structure assembly includes a first plate and a second plate, at least one of these plates having one or more microgrooves, joined each other by means of an adhesive composition.
The main problem of the biomedical devices obtained by assembling different components of different materials by adhesive compositions relates to the reduction of the adhesion strength under aging, in particular when different materials (like metals, silicon, plastics, or glass) are contacting each other and are exposed to mechanical and thermal stresses.
Moreover, the components of the biomedical devices described in the art, in particular in the microelectronic and microhydraulic fields, must be biocompatible with the biological substances. Accordingly, the component materials should not hold the biological substances on their surface and should not release any contaminant substance into the biological fluid.
Additionally, the component material surface should have a high wettability to allow an easy diffusion of the biological fluids, typically having an aqueous base, into the biomedical device. The wettability is even more important in devices containing microhydraulic conduits wherein the flow of the fluids depends on capillarity forces and interactions between the fluid and the contacting surface.
Surface treatments are known in the art to reduce the chemical and physical interactions between the material surfaces and the biological fluids, such as, for example, plasma treatment, corona treatment, or film coating. However, plasma and corona treatments have a limited duration over time. Film coating treatments which alter the material surface, can also make difficult the subsequent adhesion of the components and its strength under aging.
The assembling of biomedical device has another problem related to the lack of planarity of the surfaces to be assembled. The lack of planarity can be due to a bending of the component or to scratches on its surface. High amounts of conventional liquid adhesive compositions are required to cover the lack of planarity, but this easily promotes the straining of the liquid adhesive compositions into the cavities and voids of the microhydraulic channels of the biomedical devices, with the consequent occlusion thereof. The very same problem arises even using low amounts of conventional liquid adhesive compositions and hot pressure or using solid adhesive compositions dissolved in a proper solvent. In the latter case, a further problem of damages to the plastic material of the biomedical device arises, due to the attack of the solvent.